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ZJU-6, a novel derivative of Erianin, shows potent anti-tubulin polymerisation and anti-angiogenic activities

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Summary

ZJU-6 was designed to enhance anti-angiogenesis and anti-tumour activity of its parent compound Erianin, a clinic anti-tumour agent. This study investigated the detailed biological mechanism of ZJU-6 in comparison with that of Erianin. Both ZJU-6 and Erianin substantially reduced cell viability and induced apoptosis in human cancer cell lines. Profound G2/M cell arrest was observed 24 h after treatment of MCF-7 cells with ZJU-6 (≥ 2.5 μM) or Erianin (≥ 0.1 μM); being consistent with mitotic collapse. 0.5 μM of Erianin or ZJU-6 failed to stabilise tubulin. Pre-G1 MCF-7 cell accumulating 24 h post treatment indicated apoptosis. Caspase-3 activity, PARP cleavage and Annexin V + ve /PI -ve populations correlate the apoptotic destiny of cells exposed to either ZJU-6 or Erianin. Furthermore ZJU-6 showed potent anti-angiogenetic property and demonstrated radical scavenging capacity. Due to its potent anti-proliferative, pro-apoptotic and anti-angiogenic activities ZJU-6 is an attractive chemotherapeutic agent to be developed.

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Acknowledgments

This work has been supported by The Royal Society, UK (grant RC2617) and NSFC, China

Conflicts of interest

No potential conflicts of interest are disclosed.

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Authors and Affiliations

  1. School of Pharmacy and Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham, NG7 2RD, UK

    Frankie Lam, Tracey D. Bradshaw, Scott Roberts & Shudong Wang

  2. Department of Chemistry, Zhejiang University, Hangzhou, 310027, People’s Republic of China

    Hui Mao & Yuanjiang Pan

Authors
  1. Frankie Lam
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  2. Tracey D. Bradshaw
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  3. Hui Mao
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  4. Scott Roberts
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  5. Yuanjiang Pan
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  6. Shudong Wang
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Corresponding author

Correspondence to Shudong Wang.

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Lam, F., Bradshaw, T.D., Mao, H. et al. ZJU-6, a novel derivative of Erianin, shows potent anti-tubulin polymerisation and anti-angiogenic activities. Invest New Drugs 30, 1899–1907 (2012). https://doi.org/10.1007/s10637-011-9755-9

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  • DOI: https://doi.org/10.1007/s10637-011-9755-9

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